CD14++CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients

Heine, Gunnar H.; Ulrich, Christof; Seibert, Eric; Seiler, Sarah; Marell, Jeannette; Reichart, B; Krause, Matthias; Schlitt, Axel; Köhler, Hans; Girndt, Matthias

doi:10.1038/sj.ki.5002744

Cited by 194 publications

(198 citation statements)

References 37 publications

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“…This result was in accordance with recent studies [33][34][35] in patients on dialysis and with chronic kidney disease, which suggested an elevated risk of cardiovascular events when in the presence of a higher level of the intermediate monocytes. This finding also indicated that traditional risk factors accounted for only a small fraction of the excess risk.…”

Section: Discussionsupporting

confidence: 82%

Intermediate Monocytes Lead to Enhanced Myocardial Remodelling in STEMI Patients With Diabetes

Zhang

2015

Int. Heart J.

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SummaryThis study aimed to evaluate the potential associations of intermediate monocytes (CD14 ++ CD16 + ) with myocardial remodelling in ST segment elevation myocardial infarction (STEMI) patients with diabetes.A total of 67 STEMI patients with diabetes were enrolled. The control group consisted of 65 STEMI patients without diabetes. All patients received emergency medical services for reperfusion therapy in less than 12 hours after onset of AMI. Blinded to patient clinical characteristics, monocyte subset analysis was performed using flow cytometry immediately after admission. mRNA of Chemokine Decoy Receptor D6 in each subset of monocytes was validated by Q-PCR. Expression of CCL2 in patient plasma was determined with an Elisa kit. Infarct size and left ventricular ejection fraction (LVEF) were measured using 3-dimensional echocardiography 3 days and 6 months after AMI. The incidences of recurrent cardiovascular events and death in each group were measured using the Kaplan-Meier estimator in follow-up during the next 24 months. Cox proportional-hazard models were further used to analyze the relationship of monocyte cell counts and event-free survival after adjusting for confounding factors.The number of circulating intermediate monocytes was significantly correlated with LVEF% and infarct size (r = -0.32; P = 0.008; r = 0.57, P < 0.001) in STEMI patients with diabetes compared with those without diabetes 6 months after AMI. Chemokine Decoy Receptor D6 transcript levels were lower in intermediate monocytes of STEMI patients with diabetes compared to the subsets in STEMI patients without diabetes (P < 0.001). Higher levels of CCL2 (pg/mL) were observed in STEMI patients with diabetes compared to STEMI patients without diabetes (P < 0.001). During a mean follow-up period of 24 ± 1 month, recurrent cardiovascular events or death occurred in 23 patients belonging to the STEMI with diabetes group and 10 belonging to the control group. Univariate Kaplan-Meier analysis revealed that counts of the intermediate monocytes according to median showed statistical significance in STEMI patients with diabetes (P = 0.010). After full adjustment for confounding factors, the cells were found to remain independently related to recurrent cardiovascular events or death in this group (P = 0.004, 95% CI: 1.62-12.49).Intermediate monocytes were associated with LV remodelling in STEMI patients with diabetes. The cells were predictive for recurrent cardiovascular events or death in these patients. A low level of D6 mRNA in the intermediate monocytes of STEMI patients with diabetes and high level of CCL2 in these patients may partially explain the causality. (Int Heart J 2015; 56: 22-28)

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Section: Discussionsupporting

confidence: 82%

Intermediate Monocytes Lead to Enhanced Myocardial Remodelling in STEMI Patients With Diabetes

Zhang

2015

Int. Heart J.

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“…Monocytes were gated in a SSC/CD86 ϩ dotplot identifying monocytes as CD86 ϩ cells with monocyte scatter properties. Subsets of Mo1, Mo2, and Mo3 monocytes were defined as reported earlier (11). Absolute numbers of monocyte subpopulations were calculated from the relative frequency among the monocytes as measured into the SSC/CD86 gate multiplied by the monocyte number determined by a differential cell count.…”

Section: Laboratory Methodsmentioning

confidence: 99%

Monocyte Angiotensin Converting Enzyme Expression May Be Associated with Atherosclerosis Rather than Arteriosclerosis in Hemodialysis Patients

Ulrich

Seibert

Heine

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Circulating monocytes can be divided into functionally distinct subpopulations according to their surface expression of CD14 and CD16. Monocytes with high-level expression of both antigens (CD14 ϩϩ CD16 ϩ , Mo2 cells) are associated with cardiovascular morbidity and mortality in hemodialysis patients. These cells express angiotensin converting enzyme (ACE) on their surface. They are involved in the association of chronic inflammation and cardiovascular disease in kidney patients. Cardiovascular morbidity results from atherosclerosis (plaque-forming, vessel occluding disease) and arteriosclerosis (loss of arterial dampening function). It is unknown whether ACE-expressing proinflammatory monocytes are related to atherosclerosis, arteriosclerosis, or both.Design, setting, participants, & measurements During baseline examination for a prospective study on monocyte ACE expression and mortality, 60 chronic hemodialysis patients of an academic outpatient center were screened for atherosclerosis by carotid artery ultrasound, for arteriosclerosis by pulse pressure measurement, and for ACE expression on Mo2 cells by flow cytometry.Results ACE expression on Mo2 monocytes was significantly higher in patients with severe compared with those with little or no carotid atherosclerosis. Mo2 ACE correlated with a score to semiquantify atherosclerosis and remained a significant predictor of carotid plaques in multivariate analysis including the other univariately associated variables of age, hemoglobin A1c, and albumin. Mo2 ACE was not related to pulse pressure.Conclusions ACE expression on Mo2, although being a known predictor of mortality and cardiovascular disease in end-stage renal disease patients, may act via enhancement of atherosclerosis rather than arteriosclerosis.

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“…Both in vitro and animal studies suggested a selective role of distinct monocyte subpopulations in the development of atherosclerosis (15). In dialysis patients, Heine et al (16) showed that CD14 2ϩ CD16 ϩ monocytes but not total monocyte numbers predicted cardiovascular events. In that study, across increasing CRP and CD14 2ϩ CD16 ϩ monocyte tertiles, the death count became increasingly higher ( Figure 1A).…”

Section: Inflammatory Milieu Synergistically Stimulates Cytokine Prodmentioning

confidence: 99%

Persistent Inflammation as a Catalyst for Other Risk Factors in Chronic Kidney Disease

Carrero¹,

Stenvinkel²

2009

Clinical Journal of the American Society of Nephrology

180

131

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Because inflammation by now is a "traditional" finding that predicts poor outcome and cardiovascular events in the vast majority of patients with ESRD, it could be argued that inflammatory biomarkers should not longer be considered "novel" risk factors. In this review, we forward the hypothesis that, in addition to putative direct proatherogenic effects, persistent inflammation may serve as a catalyst and, in the toxic uremic milieu, modulate the effects of other concurrent vascular and nutritional risk factors. We discuss some recent observational studies, suggesting that the presence of persistent inflammation magnifies the risk for poor outcome via mechanisms related to self-enhancement of the inflammatory cascade and exacerbation of both the wasting and the vascular calcification processes. Because persistent inflammation may be the silent culprit of other commonly observed pathophysiologic alterations in chronic kidney disease, it is imperative that inflammatory markers be regularly monitored and therapeutic attempts be made to target persistent low-grade inflammation in this patient group.

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CD14++CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients

Cited by 194 publications

References 37 publications

Intermediate Monocytes Lead to Enhanced Myocardial Remodelling in STEMI Patients With Diabetes

Intermediate Monocytes Lead to Enhanced Myocardial Remodelling in STEMI Patients With Diabetes

Monocyte Angiotensin Converting Enzyme Expression May Be Associated with Atherosclerosis Rather than Arteriosclerosis in Hemodialysis Patients

Persistent Inflammation as a Catalyst for Other Risk Factors in Chronic Kidney Disease

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